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Cetuximab and Radiation Therapy for Surgically Resectable Esophageal and Gastroesophageal (GE) Junction Carcinomas

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Walther Cancer Institute
Information provided by (Responsible Party):
Nasser Hanna, M.D., Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT00319735
First received: April 27, 2006
Last updated: March 28, 2016
Last verified: March 2016

April 27, 2006
March 28, 2016
April 2006
January 2009   (final data collection date for primary outcome measure)
Complete Pathologic Response (pCR) [ Time Frame: 36 months ] [ Designated as safety issue: No ]

To evaluate complete pathologic response rate in patients with esophageal and GE junction carcinomas.

Complete pathologic response (pCR) is defined as the absence of tumor cells on the resected specimen in the esophagus and/or GE junction.

· To evaluate complete pathologic response rate in patients with esophageal and GE junction carcinomas
Complete list of historical versions of study NCT00319735 on ClinicalTrials.gov Archive Site
  • Complete Pathological Response Rate for Patients Who Underwent Esophagectomy. [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]

    To evaluate complete pathologic response rate in patients with esophageal and GE junction carcinomas that underwent esophagectomy.

    Complete pathologic response (pCR) is defined as the absence of tumor cells on the resected specimen in the esophagus and/or GE junction.

  • Time to Relief of Dysphagia [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    To evaluate time to relief of dysphagia in patients with esophageal and GE junction carcinomas receiving preoperative radiation and cetuximab
  • Evaluate Toxicity [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
    To evaluate the overall toxicities of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas
  • Perform Exploratory Molecular Correlates. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    To perform exploratory molecular correlates to determine the mechanisms of response and resistance to cetuximab and radiation therapy.
  • Complete and Partial Response Rate for Patients by Disease Stage: IIA [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    To evaluate complete and partial response rate of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas
  • Complete and Partial Response Rate for Patients by Disease Stage: IIB [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    To evaluate complete and partial response rate of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas
  • Complete and Partial Response Rate for Patients by Disease Stage: III [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    To evaluate complete and partial response rate of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas
  • Complete and Partial Response Rate for Patients by Histology: Adenocarcinoma [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    To evaluate complete and partial response rate of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas
  • Complete and Partial Response Rate for Patients by Histology: Squamous Cell [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    To evaluate complete and partial response rate of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas
  • To evaluate complete and partial response rate of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas
  • To evaluate time to relief of dysphagia in patients with esophageal and GE junction carcinomas receiving preoperative radiation and cetuximab
  • To evaluate the overall toxicities of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas
  • To perform exploratory molecular correlates to determine the mechanisms of response and resistance to cetuximab and radiation therapy.
Not Provided
Not Provided
 
Cetuximab and Radiation Therapy for Surgically Resectable Esophageal and Gastroesophageal (GE) Junction Carcinomas
A Pilot Study With Cetuximab and Radiation Therapy for Patients With Surgically Resectable Esophageal and GE Junction Carcinomas: Hoosier Oncology Group Study (GI05-92)

The interaction of epidermal growth factor receptor (EGFR) inhibitory agents such as cetuximab combined with radiation shows promising results. EGFR inhibitory agents also enhance radiation-induced apoptosis and inhibit radiation induced damage repair. These interactions may represent the principle effects that contribute to the synergy between EGFR and radiation.

This trial will investigate the feasibility and activity of this combination in patients with surgically resectable disease.

OUTLINE: This is a multi-center study.

  • Cetuximab 400 mg/m2 IV over 120 minutes Day -14 (Loading Dose)
  • Cetuximab 250 mg/m2 IV over 60 minutes, day -7.
  • Cetuximab 250 mg/m2 IV over 60 minutes, days 1, 8, 15, 22, 29 and 36.
  • External beam radiation therapy, beginning on day 1, 4500 cGy to esophagus with boost of 540 cGy at 180 cGy per fraction for 6 weeks.
  • Surgical resection of primary tumor and adjacent mediastinal and/or celiac lymph nodes by a transthoracic approach after satisfactory hematologic and functional recovery within 8 weeks of completion of radiation therapy.
  • For patients who give their consent, fresh frozen tissue will be obtained per EUS at baseline, per EUS 2 weeks after the initiation of cetuximab, and at the time of surgery for pathology submission.
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Esophageal Cancer
  • Procedure: Radiation Therapy
    External beam radiation therapy, beginning on day 1, 4500 cGy to esophagus with boost of 540 cGy at 180 cGy per fraction for 6 weeks
  • Procedure: Surgery
    Surgical resection of primary tumor and adjacent mediastinal and/or celiac lymph nodes by a transthoracic approach after satisfactory hematologic and functional recovery within 8 weeks of completion of radiation therapy
  • Procedure: Tissue Sample
    For patients who give their consent, fresh frozen tissue will be obtained per EUS at baseline, per EUS 2 weeks after the initiation of chemotherapy, and at the time of surgery for pathology submission
Experimental: Investigational Treatment
  • Cetuximab 400 mg/m2 IV over 120 minutes Day -14 (Loading Dose)
  • Cetuximab 250 mg/m2 IV over 60 minutes Day -7
  • Cetuximab 250 mg/m2 IV over 60 minutes Days 1, 8, 15, 22, 29 and 36
  • Combined with radiation therapy for six weeks.
  • Surgery for esophageal resection after 6 to 8 week rest period.

Subjects who consent will provide tissue samples.

Interventions:
  • Procedure: Radiation Therapy
  • Procedure: Surgery
  • Procedure: Tissue Sample
Becerra CR, Hanna N, McCollum AD, Becharm N, Timmerman RD, DiMaio M, Kesler KA, Yu M, Yan T, Choy H. A phase II study with cetuximab and radiation therapy for patients with surgically resectable esophageal and GE junction carcinomas: Hoosier Oncology Group G05-92. J Thorac Oncol. 2013 Nov;8(11):1425-9. doi: 10.1097/JTO.0b013e3182a46c3b.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
41
January 2009
January 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Pathological diagnosis of either squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction.
  • Clinical stage IIA, IIB or III without metastatic disease
  • Patients must have documented EGFR status or have tumor tissue available for assessment of EGFR status by IHC
  • Patients must be surgical candidates as determined by surgical consult.
  • Patients must agree to surgery.
  • ECOG performance status 0 or 2
  • Absolute neutrophil count (ANC) > 1,000 mm3
  • Platelet count > 75,000 mm3· Hemoglobin > 10g/dL
  • Bilirubin < 2.5 X upper limit of normal
  • AST (SGOT) or ALT (SGPT) < 5.0 ´ upper limit of normal
  • Creatinine < 2.0 X upper limit of normal

Exclusion Criteria:

  • No history of or current brain metastasis.
  • No significant history of uncontrolled cardiac disease; i.e. uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
  • No history of interstitial pneumonitis or pulmonary fibrosis, or suspicion of interstitial pneumonitis or pulmonary fibrosis on imaging.
  • No concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s).
  • No prior use of radiation or chemotherapy for cancer of the esophagus or GE junction
  • No prior therapy that specifically and directly targets the EGFR pathway (such as kinase inhibitors and antibodies directed against the HER family receptors).
  • No prior severe infusion reaction to a monoclonal antibody.
  • No major surgery within 28 days prior to being registered for protocol therapy.
  • No clinically significant infections as judged by the treating investigator.
  • No acute hepatitis or known HIV.
  • No other active malignancies.
  • Negative pregnancy test.
  • No female patients currently breastfeeding.
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00319735
HOG GI05-92
Yes
No
Not Provided
Nasser Hanna, M.D., Hoosier Cancer Research Network
Nasser Hanna, M.D.
  • Bristol-Myers Squibb
  • Walther Cancer Institute
Study Chair: Carlos Becerra, M.D. Hoosier Oncology Group, LLC
Study Chair: Nasser Hanna, M.D. Hoosier Oncology Group, LLC
Hoosier Cancer Research Network
March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP